Chitosan/Poly (vinyl alcohol) Based Hydrogels for Biomedical Applications: A Review

Journal of Pharmacy and Alternative Medicine www.iiste.org

ISSN 2222-5668 (Paper) ISSN 2222-4807 (Online)

Vol. 2, No. 1, 2013

30

Review Article

Chitosan/Poly (vinyl alcohol) Based Hydrogels for Biomedical

Applications: A Review

Nazar Mohammad Ranjha, Samiullah Khan*

Department of Pharmaceutics, Faculty of Pharmacy, Bahauddin Zakariya University Multan-60800,

Punjab-Pakistan

*E-mail of the corresponding author: [email protected], Tel: +92-333-9952522

Received Date: 17 January 2013 Accepted Date: 24 February 2013

Abstract

The present review aims to give a closer look of hydrogels based on chitosan and poly (vinyl alcohol) and

to discuss their potential biomedical applications in drug delivery system. Various investigations based on

chitosan/poly (vinyl alcohol) carried out recently by researchers have been reported in this review.

Moreover different chemical and physical crosslinking methods used for hydrogels formulations have been

summarized and discussed in this overview. Different characterization tools including Fourier transform

infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermo

gravimetric analysis (TGA), differential scanning calorimetry (DSC) and rheological analysis used by

researchers have also been reported in this review.

Keywords: Hydrogels, Chitosan, Poly (vinyl alcohol), Physical crosslinking, Chemical crosslinking

1. Introduction

Since a large number of active compounds that claims as therapeutics have been discovered, but a very few

candidates have shown medical characteristics. A number of factors could be attributed to the poor activity

of these compounds such as low bioavailability, the rate and extent at which drug reaches the target site and

the response of the receptors at the target tissue to the drug. Various techniques have been implied to

prepare biocompatible and biodegradable formulations using natural polymers that are degradable through

enzymatic reactions, or using synthetic polymers that contain hydrolysable groups (Bhattarai et al., 2010).

In the last few years, a huge study has been carried out on biomaterials based on polysaccharides.

Polysaccharides such as chitosan, starch, dextran and gallan are the biological polymers obtained from

various animal and vegetal sources. These biopolymers have received various advantages in the recent

years, as researchers continue to investigate and modify these biomaterials for demanding needs of

biomedical applications in the drug delivery. It was also found that when they are joined to synthetic

polymers such as poly (vinyl alcohol) (PVA) or poly (acrylic acid) (PAA), they increase the mechanical

properties of the resulting materials (Cascone et al., 2001).

Chitosan is a linear polysaccharide of β-[1- 4]-linked 2-acetamido- 2-deoxy-D-glucopyranose and

2-amino-2-deoxy-D-glucopyranose. Commercially it is obtained by alkaline deacetylation of chitin, a

structural component in the exoskeleton of crustaceans and insects. It is abundant in nature and considered

as second abundant biopolymer after cellulose (Berger et al., 2004). Table 1 indicates some principal

sources of chitin.

Chitosan is playing an ideal role and attaining a great interest for controlled drug delivery. Due to its

biocompatible and biodegradable properties, it has various pharmaceutical and biomedical applications

such as implantation or injection, topical ocular application. Moreover it is metabolized inside the body by

some human enzymes i.e. lysozyme and so considered as biodegradable. Chitosan also has bacteriostatic

effects and so enhance wound healing (Costa-Junior et al., 2009).Fig 1 shows structure of cellulose, chitin

and chitosan.

mailto:[email protected]



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Figure: 1 Structure of Cellulose, Chitin and Chitosan

Table 1: Principal sources of Chitin

Organisms Chitin contents %

Insects True fly 51.2

Sulphur butterfly 66.3

Fungi Aspergillus niger 40.0

Mucorrouxii 42.8

Crustacea Shrimp 67.7

Crab 70.6

Lobster 67.6

Poly (vinyl alcohol) (PVA) is a semi-crystalline synthetic polymer which has been studied intensively

because of its various desirable properties such as high hydrophilicity, good film forming, process ability,

biocompatibility, gel forming and physical properties, good film forming and good chemical resistance.

These properties of poly (vinyl alcohol) made its wide use in the production of paper, paints, glues, clothes,

pharmaceutical products, ceramics and building materials (Hernandez et al., 2004). Table 2 shows physical

properties of polyvinyl alcohol (PVA).

Chitosan combined with other polymers offered the researchers a new window for changing the desire of

interest. Figure 2 indicates the structure of poly (vinyl alcohol) (PVA).



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Table 2: Physical Characteristics of Poly (vinyl alcohol) (PVA)

S.NO. Property Result

1 Appearance Cream colored granular

powder

2 Odour Odourless

3 Taste Tasteless

4 Solubility in water Soluble

5 Solubility in Alcohol Slightly Soluble

6 Solubility in organic solvents Insoluble

7 Melting Point 180 to 190°C

8 Molecular weight Between 26,300 and 30,000

9 Degree of hydrolysis 86.5 to 89%.

Hydrogels are crosslinked macromolecular networks swollen in water or biological fluids and have the

ability to retain substantial amount of solvent in its structure without undergoing to dissolve (Guanghua et

al., 2008). The water absorbing ability of hydrogels is provided by certain hydrophilic functional groups

(such as -OH, -COOH, - CONH2, -SO3H) in the polymer chains (Chandra et al., 2013). Due to the

presence of these certain functional groups in the polymer chains, hydrogels are considered to be sensitive

to the conditions of the surrounding environment such as temperature, pH or ionic strength of the swelling

solutions or even to the presence of a magnetic field or ultraviolet light, due to which they are referred to as

“intelligent materials” or “smart materials” (Sadeghi et al., 2011). Hydrogels have many applications in

the biomedical field which includes contact lenses, wound dressing, catheters, coating for sutures, artificial

corneas and electrode sensors (Pal et al., 2007). Hydrogels can be classified into several classes based on

the nature of network such as covalently crosslinked networks, entangled networks and networks formed by

secondary interactions (Berger et al., 2004).The present review is made to focus on the current applications

of Chitosan/Poly (vinyl alcohol) based hydrogels and to discuss the future prospects of biopolymers

combined with synthetic materials for the pharmaceutical and medical applications in the drug delivery

(Kumar et al., 2000).

Figure 2: Structure of Poly (vinyl alcohol) (PVA)



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2. Hydrogel Crosslinked Network

Different methods of crosslinking have been used in hydrogel formulations. Generally physical and

chemical methods have been applied commonly. In chemically crosslinked hydrogels, crosslinking can be

produced by covalent bonds between different polymer chains. While in physically crosslinked hydrogels,

physical interactions exist between different polymer chains which prevent them from dissolution [Hennink

et al., 2002]. These two methods are discussed below in detail.

2.1 Chemically crosslinked hydrogels

Chemically crosslinked networks are also called permanent or chemical hydrogels (Chandra et al., 2013).

Chemical crosslinking is a suitable method to generate permanent hydrogel networks by implying covalent

bonding between different polymer chains. Chemically crosslinked networks can be produced by chemical

reactions between different available functional groups and crosslinkers that can generate number of

linkages among the available groups including Schiff base formation and amine carboxylic acid bonding

(Hoare et al., 2008; Berger et al., 2004). More particularly these networks can be produced by using low

molecular weight crosslinkers, photosensitive agents or enzymes catalyzed reactions and polymer-polymer

interactions between activated functional groups. Genipin, the new crosslinking agent is a naturally derived

chemical obtained from the gardenia that has been proved to be one biocompatible cross-linking agent (Jin

et al., 2004). Genipin has been shown to bind biological tissues (Sung et al., 2001) and biopolymers, such

as gelatin and chitosan leading to covalent coupling. It works as an effective cross-linking agent for

polymers containing amino groups and is much less cytotoxic than glutaraldehyde (Sung et al., 1999).

In photo crosslinking, polymer mixtures that can form hydrogels can be developed by using photosensitive

functional groups. The polymer can form crosslinking with these reactive groups upon irradiation with UV

light (Ono et al., 2000). In polymer-polymer crosslinking method, pre-functionalized polymer chains with

reactive functional groups are required in order to eliminate the use crosslinker molecule during gelation. In

this type of crosslinking, covalent linkages can be formed that mainly depend upon the desired speed of

crosslinking and selection of targeted reactive functional groups (Tan et al., 2009).

2.2 Physically crosslinked hydrogels

The interest towards physically crosslinked gels has been increased in recent years due to the elimination of

crosslinking agent in these hydrogels (Kumar et al., 2000). Physically crosslinked hydrogels mainly

demands two conditions: (1) inter-chain interactions in the molecular network must be strong enough to

form semi-permanent junction points (2) The network must allow the penetration of maximum water

molecule inside the polymer network (Berger et al., 2004). Several methods have been reported for the

preparation of physically crosslinked hydrogels but mainly includes; crosslinking by ionic interactions,

crosslinking by crystallization and crosslinking by stereo complex formation (Kumar et al., 2000).

Crosslinking by ionic interactions occur only between oppositely charged groups of polymers or monomers

which formulate the hydrogel network. Chitosan which contains cationic amino groups forms ionic

complexation of mixed charge system with small anionic molecules such as phosphates, citrates, sulphates

(Shu et al., 2002) and also with the metal anions such as Mo(VI),Pt (II), Pd (II) (Dambies et al., 2001).

Chitosan make linkage with the anions and other small molecule through protonated amino groups, while in

case of metal ions, it forms coordinate-covalent bonds rather than electrostatic repulsion with polymer

(Brack et al., 1997).

Crosslinking by crystallization leads to gel formation gradually, when stored at room temperature. However

hydrogels formed by means of crystallization may be of low mechanical strength. Polyvinyl alcohol which

is water soluble polymer forms gels by crystallization method when its aqueous solution is stored at room

temperature. This gel formation is mainly attributed due to formation of PVA crystallites which act as

physical crosslinking sites in the network (Yokoyama et al., 1986).

In recent years hydrogels based on stereo complex formation were reported for drug delivery system. It has

been investigated that stereo complex formation occurs in blends of triblock copolymers of

PLLA–PEG–PLLA and PDLA–PEG–PDLA (Lim et al., 2000).



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3. Chitosan/Poly (vinyl alcohol) based hydrogels

Hydrogels based on chitosan and polyvinyl alcohol has various pharmaceutical and biomedical applications

in drug delivery system. Huge efforts and large studies have been made to prepare the Chitosan/Poly (vinyl)

alcohol hydrogels and their potential for controlled drug delivery has been extensively studied by research

workers. The literature related to Chitosan/Poly (vinyl alcohol) based hydrogels is reviewed as under;

3.1 Preparation and characterization of Chitosan/Poly (vinyl alcohol) based hydrogels

Vrana et al., 2008 synthesized PVA/Chitosan hydrogels crosslinked with KOH/Na2SO4coagulation bath by

freeze/thaw cycle’s technique. Authors evaluated the effect of number of freeze/thaw cycles on cell

behaviour. Authors modified hydrogels surface using collagen type I adsorption and seeded with bovine

aortic vascular smooth muscle and endothelial cells. Authors found that marked increase in hydrophilicity,

surface morphology and protein adsorption may occur by increasing the number of freeze/thaw cycles

(Vrana et al., 2008).

Mathews et al., 2008 prepared poly (vinyl alcohol)/chitosan hydrogels by freeze/thaw cycles method and

investigated the effect of type of chitosan (water soluble or insoluble) and freeze/thaw cycles on the

mechanical and morphological properties of the hydrogels. Authors characterized these hydrogels by

scanning electron microscope (SEM), uniaxial testing, and a biaxial tubular vessel inflation experiment

(Mathews et al., 2008).

Pei et al., 2008 synthesized chitosan/polyvinyl alcohol/alginate composite film by the casting/solvent

evaporation method for wound healing. Authors loaded ornidazole (OD) as model drug in hydrogels and

studied its potential capacity for use in wound healing. Authors studied the in vitro antibacterial effects of

the loaded drug and characterize the gels by FTIR and scanning electron microscope (SEM) (Pei et al.,

2008).

Tang et al., 2009 prepared thermo sensitive chitosan/polyvinyl alcohol hydrogels by two synthetic routes i.e.

insitue and exsitue routes. The prepared thermosensitive hydrogels contain hydroxyapatite for protein

delivery. Authors subjected these gels to characterization by Fourier-transform infrared spectroscopy

(FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and rheological analysis (Tang et

al., 2009).

Bahrami et al., 2003 synthesized Poly (vinyl alcohol)/chitosan blended films by casting technique using

glutaraldehyde as crosslinking agent. Authors characterized the mechanical and physical properties of

blended films including water uptake, surface tension, contact angle and tensile properties in the dry and

wet states (Bahrami et al., 2003).

Abdeen in 2011 prepared blend semi-synthetic hydrogel film composed of polyvinyl alcohol and chitosan

using glutaraldehyde as crosslinking agent by solvent-casting technique. Authors characterized these

hydrogels by FTIR spectroscopy for their intermolecular interactions between chitosan and polyvinyl

alcohol molecules (Abdeen., 2011).

Kim et al., 2003 synthesized interpenetrating polymer network (IPN) hydrogels consisting of poly (vinyl

alcohol)/chitosan by UV irradiation method. Authors investigated the change in swelling of poly (vinyl

alcohol)/chitosan (IPN) hydrogels in response to external environment such as temperature and pH (Kim et

al., 2003).

Guanghua et al., 2008 prepared physically crosslinked composite hydrogels consisting of poly (vinyl

alcohol)/chitosan (CS) by cyclic freezing/thawing techniques. Authors characterized these hydrogels by

infrared spectra (IR), scanning electron microscope (SEM) and differential scanning calorimetry (DSC)

(Guanghua et al., 2008).

Gunasekaran et al., 2006 synthesized pH-Sensitive Chitosan–Poly (vinyl alcohol) Hydrogels in different

molar ratios using glutaraldehyde as crosslinking agent. Authors in this study investigated the effect of pH

of medium and salt concentrations on the swelling properties of these hydrogels (Gunasekaran et al., 2006).

Khurma et al., 2006 prepared semi-interpenetrating polymeric networks consisting of chitosan and poly



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(vinyl alcohol) of different ratios of constituent’s crosslinked by genipin, a naturally occurring crosslinking

agent having no toxicity. Authors subjected these hydrogels to characterization by differential scanning

calorimetry (DSC) (Khurma et al., 2006).

Cascone et al., 1999 prepared poly (vinyl alcohol) based hydrogels by freezing-thawing technique using

varying quantities of dextran and chitosan. Authors characterized these hydrogels by scanning electron

microscope (SEM), differential scanning calorimetry (DSC) and dynamic-mechanical analysis (Cascone et

al., 1999).

Sung et al., 2010 synthesized cross-linked hydrogel films consisting of polyvinyl alcohol and chitosan by

freeze and thawing method. Authors evaluated in vivo wound healing effect, histopathology, release, in

vitro protein adsorption and gel properties. Authors loaded the gel with minocycline and observed its

healing effect by subjecting it to wound healing test (Sung et al., 2010)

Yang et al., 2008 prepared hydrogels consisting of poly (vinyl alcohol) (PVA) and water soluble chitosan

(ws-chitosan) for wound dressing by combined γ-Irradiation and freeze-thawing technique. Authors

compared the properties of these gels prepared by combined technique to those prepared by freeze-thawing

and irradiation alone. Authors characterized these gels by scanning electron microscope (SEM) (Yang et al.,

2008).

Mincheva et al., 2007 developed bicomponent nanofibers composed of N-carboxyethylchitosan and poly

(vinyl alcohol) by electro spinning technique using mixed aqueous solutions of the polymers. Authors

studied the surface morphology of nanofibers by subjecting these to scanning electron microscope (SEM)

(Mincheva et al., 2007).

Rao et al., 2006 prepared novel pH-sensitive interpenetrating polymeric network (IPN) microgels

consisting of chitosan, acrylamide-grafted-poly(vinyl alcohol) and hydrolyzed acrylamide grafted-poly

(vinyl alcohol) using glutaraldehyde as crosslinking agent. Authors loaded cefadroxil as model drug and

used these microgels for the controlled release of drug. Authors characterized these microgels by Fourier

transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and differential scanning

calorimetry (DSC) (Rao et al., 2006).

Yang et al., 2004 used chitosan and poly(vinyl alcohol) in various ratio to prepare blended membranes

using glutaraldehyde as crosslinking agent. Authors conducted permeability studies of creatinine, 5-FU and

vitamin B12, through these blended membranes. Authors characterized these membranes by Fourier

transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), dynamic mechanical

analysis (DMA)and thermogravimetric analysis (TGA)(Yang et al., 2004).

Masci et al., 2003 prepared poly (vinyl alcohol) (PVA) physical hydrogels using different derivatives of

lactosilated chitosan of varying molecular weight by repeated freeze-thawing cycles technique of aqueous

solutions of polymers. Authors characterized these hydrogels by thermogravimetric analysis (TGA),

scanning electron microscopy (SEM) and differential scanning calorimetry (DSC) (Masci et al., 2003).

Kim et al., 2003 synthesized interpenetrating polymer networks (IPN) hydrogels consisting of Poly (vinyl

alcohol) (PVA)/chitosan by UV irradiation method. Authors measured swelling behaviour of these IPNs

hydrogles at various temperature and humidity levels (Kim et al., 2003).

Yang et al., 2007 prepared Chitosan/Poly (vinyl alcohol) blending Hydrogel and used it for surface coating

of segmented polyurethane to reduce catheter related complications. Authors used Fourier transform

infrared spectroscopy (FTIR) to confirm surface modifications at every step (Yang et al., 2007).

Costa-Junior et al., 2009 prepared blended films composed of chitosan and poly (vinyl alcohol) chemically

crosslinked with glutaraldehyde in this work for use in skin tissue repairing. Authors used Fourier

Transform Infrared spectroscopy (FTIR) and scanning electron microscopy (SEM/EDX) analysis to study

microstructure and morphology of the hydrogel films (Costa-Junior et al., 2009).

Costa-Junior et al., 2009 prepared glutaraldehyde crosslinked novel polymer blends of chitosan/poly (vinyl

alcohol) for variety of biomedical applications. Authors characterized these blended films through X-ray

diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy analysis to study



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crystallinity, structure and morphology of the blended hydrogels (Costa-Junior et al., 2009).

Wang et al., 2004 synthesized pH sensitive semi-interpenetrating polymeric network consisting of chitosan

and poly (vinyl alcohol) using glutaraldehyde as crosslinking agent. Authors subjected these gels to Fourier

transform infrared spectroscopy (FTIR) for structure confirmation (Wang et al., 2004).

3.2 Applications

Chitosan is versatile biopolymer that is inexpensive and contains some important physiological properties

such as biodegradable, biocompatible, non-toxic, non-allergenic and mucoadhesive properties for mammals.

These properties of chitosan make it suitable to be used in various fields including biomedicine, agriculture,

cosmetics, environmental protection, food, fibre industries and wastewater management (Kumar et al.,

2004).

3.2.1 Pharmaceutical and medical applications

Over the last three decades, chitosan and its derivatives have been reported for huge range of biomedical

applications in pharmaceutical formulations and drug delivery system.

3.2.1.1 Wound healing

There are many clinical cases suggested that chitosan based materials accelerates wound healing. It was

investigated that chitosan granules could induce faster regeneration of normal skin due to increased

vascularization in open wounds. Chitosan is believed to have role in tissue growth and differentiation in

tissues in wound healing. Table 3 indicates some commercially available haemostatic dressings based on

chitosan (Shigemasa et al., 1996).

Table 3: Some commercial hemostatic dressings based on chitosan

Commercial Name Company Materials and functions

HemCon® HemCon Freeze-dried chitosan acetate salt, for

emergency use to stop bleeding

Chitoflex® HemCon antibacterial, biocompatible wound dressing

prepared to be placed into a wound area to

control moderate to severe bleeding

Chitoseal® Abbott Based on chitosan, backed with cellulose

coating used for wounds bleeding

Clo-Sur® Scion Based on chitosan, a pressure pad applied

topically to accelerate wound healing

TraumaStat® Ore-Medix Freeze-dried chitosan containing highly

porous silica

Syvek-Patch® Marine Polymer

Technologies

Composed of fully acetylated, high

molecular-weight chitin in a crystalline, three

dimensional beta structure array, and

separated from the centric diatom

Thalassiosirafluviatilis. It is believed to be 7

times quick in achieving haemostasis than

fibrin glue.

BST-CarGel® Biosyntech company chitosan-glycerophosphate hydrogels, a

biodegradable gel used for cartilage repair



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3.2.1.2 Subcutaneous delivery

Chitosan based materials have been widely used in the field of subcutaneous delivery and implantable

devices due to its lack of immunogenicity and inflammation. As chitosan hydrogels are biodegradable in

nature so these systems require no surgical removal after implantation and successfully release therapeutic

payload inside the body (Khor et al., 2003).

3.2.1.3 Anticancer properties

In traditional drug delivery systems such as microcapsule, gel system or microspheres, drugs are usually

loaded by passive absorption, which keeps the drug loading capacity in limits. Chitosan hydrogels based

delivery systems have shown an ideal area of interest for delivery of local chemotherapeutic agents.

Chitosan matrices have been successfully loaded with radioisotopes and used for controlled exposure.

Chitosan based hydrogels have been used for breast cancer, brain tumour, localized solid tumours, primary

and secondary osteosarcoma, osteolysis and lung metastasis (Azab et al., 2007; Lesniak et al., 2004;

Ruel-Gariepy et al., 2004).

3.2.1.4 Delivery of growth factor

Chitosan based hydrogels have been extensively used in the controlled delivery of growth factors or

glycosaminogylcan (GAG) molecules in the treatment of bone, cartilage and nerve tissues. Table 4 shows

some of the examples of drugs loaded in chitosan hydrogels and their role in delivery of growth factor

(Mattioli-Belmonte et al., 1999; Suh et al., 2000; Muzzarelli et al., 1997; Park et al., 2005).

Table 4: Drug loaded in chitosan hydrogels and their applications in delivery of growth factors

Drug loaded in

Chitosan hydrogels

Applications

Chitosan hydrogels coupled with BMP-7

To improve lesion repair

Chondroitin sulfate loaded in chitosan hydrogels Cartilage formation

Platelet derived growth factor loaded in chitosan gels To improve osteoinduction

Chitosan–alginate hydrogels loaded with BMP-2 and

mesenchymal stem cells

To induce subcutaneous bone

formation

3.2.1.5 Drug delivery in gut

Due to pH sensitivity and mucoadhesive properties, chitosan based hydrogels offers significant targeting

drug release depending on the swelling of hydrogels in desired pH of medium. Chitosan based hydrogels

have been successfully implied for the delivery of therapeutic moieties to stomach because of their

significant swelling in acidic conditions (Patel et al., 1996).Some chitosan based hydrogels have been

synthesized that release the loaded drug in intestine after passing through the acidic conditions of stomach

(George et al., 2006).

3.2.1.6 Ophthalmic applications

Chitosan based formulations have wide applications in ophthalmic drug delivery systems due to their

higher retentions time as compared to conventional systems (e.g eye drops)(Felt et al., 1999). Chitosan



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based hydrogels have high bioadhesive and penetration improving characteristics, due to which they are

successfully used as drug delivery system in ophthalmic field (Thanou et al., 2001).

3.2.2 Applications in Cosmetics

Chitosan based hydrogels have been believed to have applications in transdermal drug delivery systems

because of their high water contents which provides a durable emollient effect on patient’s skin (Prausnitz

et al., 2004).Chitosan is investigated to act as film forming agent and hydrating agents in hydrogels. The

film-forming ability of chitosan helps in imparting a pleasant and emollient feeling of smoothness to the

skin and in protecting it from adverse environmental conditions. Chitosan based hydrogels have been used

for the delivery of berberine alkaloid to skin (Tsai et al., 1999).

4. Conclusion

The current review claims that researchers have made huge efforts to study chitosan/Poly (vinyl alcohol)

based formulations because of safe toxicological profile of chitosan. Due to this unique property of this

biopolymer, it has potential application in pharmaceutical and biomedical fields. For formulations of

hydrogels drug delivery system both type of crosslinking methods including physical and chemical

crosslinking have been used by researchers. For characterization, these hydrogels are subjected to different

characterization techniques. It is concluded from wide efforts and huge work of large number of research

groups in the fields of hydrogels drug delivery development and characterization that chitosan/Poly (vinyl

alcohol) hydrogels have high applications in various pharmaceutical and biomedical fields and can be

applied an ideal drug delivery in biomedical fields in future.

References

Azab AK, Kleinstern J, Doviner V, Orkin B, Srebnik M, Nissan A, Rubinstein A: Prevention of tumor

recurrence and distant metastasis formation in a breast cancer mouse model by biodegradable implant of

131I-norcholesterol. J. Control. Release 2007; 123: 116–122.

Bhattarai N, Gunn J, Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Advanced

Drug Delivery Reviews 2010; 62: 83–99.

Berger j, Reist M, Mayer JM, Felt O, Gurny R. Structure and interactions in chitosan hydrogels formed by

complexation or aggregation for biomedical applications. European Journal of Pharmaceutics and

Biopharmaceutics 2004; 57: 35–52.

Bahrami SB, Kordestani SS, Mirzadeh H, Mansoori P. Poly (vinyl alcohol) - Chitosan Blends: Preparation,

Mechanical and Physical Properties. Iranian Polymer Journal 2003; 12 (2): 139-146.

Brack HP, Tirmizi SA, Risen WM. Aspectroscopic and viscometric study of themeta ion-induced gelation

of the biopolymer chitosan.Polymer 1997; 38: 2351–2362.

Berger J, Reist M, Mayer JM, Felt O, Peppas NA, Gurny R. Structure and interactions in covalently and

ionicallycrosslinked chitosan hydrogels for biomedical applications, Eur. J. Pharm. Biopharm 2004; 57:

19–34.

Cascone MG, Barbani N, Cristallini C, Giusti P, Ciardelli G, Lazzeri L. Bioartificial polymeric materials

based on polysaccharides.J. Biomater. Sci. Polymer Edn 2001; 12(3): 267–281.

Costa-Junior ES, Barbosa-Stancioli EF, Mansur AAP, Vasconcelos WL, Mansur HS. Preparation and

characterization of chitosan/poly(vinyl alcohol) chemically crosslinked blends for biomedical applications.

Carbohydrate Polymers2009; 76: 472–481.

Chandra P, Dhaval N, Upendra DP, Bhavin B, Ghanshyam P, Dhiren D. A conceptual overview on

superporous hydrogel for controlled release drug delivery. International Journal of Pharmacy and Integrated

Life Sciences 2013; 1(2): 1-13.

Cascone MG, Maltinti S, Barbani N, Laus M. Effect of chitosan and dextran on the properties of poly(vinyl

alcohol) hydrogels. Journal of Materials science: Materials in medicine 1999; 10: 431-435.

Costa-Junior EDS, Pereira MM, Mansur HS. Properties and biocompatibility of chitosan films modified by

blending with PVA and chemically crosslinked. Journal Materials science: Materials in Medicine2009; 20:



Vol. 2, No. 1, 2013

39

553–561.

Dambies L, Vincent T, Domard A, Guibal E. Preparation of chitosan gel beads by ionotropic molybdate

gelation. Biomacromolecules 2001; 2: 1198–1205.

Felt O, Furrer P, Mayer JM., Plazonnet B, Buri P, Gurny R. Topical use of chitosan in ophthalmology:

tolerance assessment and evaluation of precorneal retention. Int. J. Pharm 1999; 180:185–193.

Guanghua HE, Hua Z, Fuliang X. Preparation and Swelling Behavior of Physically Crosslinked Hydrogels

Composed of Poly (vinyl alcohol) and Chitosan. Journal of Wuhan University of Technology-Mater2008;

23(6):816-820.

Gunasekaran S, Wang T, Chai C. Swelling of pH-Sensitive Chitosan–Poly (vinyl alcohol) Hydrogels. J.

Appl. Polym. Sci 2006; 102: 4665–4671.

George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and

chitosan—a review. J. Control. Release 2006; 114: 1–14.

Hernandez R, Sarafian A, Lopez D, Mijangos C. Viscoelastic properties of poly(vinyl alcohol) hydrogels

and ferrogels obtained through freezing–thawing cycles. Journal of Polymer2004; 46: 5543–5549.

Hennink WE, Nostrum CFV. Novel crosslinking methods to design hydrogels.Advanced Drug Delivery

Review2002; 54: 13-36.

Hoare TR, Kohane DS. Hydrogels in drug delivery: progress and challenges. Polymer 2008; 49:

1993–2007.

Jin J, Song M, Hourston DJ. Novel chitosan-based films cross-linked by genipin with improved physical

properties. Biomacromolecules 2004; 5: 162–168.

Kulkarni AR, Hukkeri VI, Sung HW, Liang HF. A novel method for the synthesis of the PEG-crosslinked

chitosan with a pH-independent swelling behavior.Macromol.Biosci 2005; 5: 925–928.

Khor E, Lim LY. Implantable applications of chitin and chitosan. Biomaterials 2003; 24: 2339–2349.

Kumar MNVR. A review of chitin and chitosan applications. Reactive & Functional Polymers 2000; 46:

1–27.

Kim SJ, Lee KJ, Kim IY, Kim SI. Swelling Kinetics of Interpenetrating Polymer Hydrogels Composed of

Poly (Vinyl Alcohol)/Chitosan. Journal of macromolecular science 2003; A40 (5): 501–510.

Khurma JR, Rohindra DR, Nand AV. Synthesis and Properties of Hydrogels Based on Chitosan and Poly

(Vinyl Alcohol) Crosslinked by Genipin. Journal of Macromolecular Science, Part A: Pure and Applied

Chemistry2006; 43: 749–758.

Kim SJ, Lee KJ, KimSI, Lee KB, Park YD. Sorption Characterization of Poly(vinyl alcohol)/Chitosan

Interpenetrating Polymer Network Hydrogels. Journal of applied polymer science 2003;90: 86–90.

Kumar MN, Muzzarelli RA, Muzzarelli C, Sashiwa H, Domb AJ. Chitosan chemistry and pharmaceutical

perspectives. Chem. Rev 2004; 104: 6017–6084.

Lim DW, Park TG. Stereocomplex formation between enantiomeric PLA–PEG–PLA triblock copolymers:

characterization and use as protein delivery microparticulate carriers, J. Appl. Polym. Sci 2000; 75:

1615–1623.

Lesniak MS, Brem H. Targeted therapy for brain tumours. Nat Rev Drug Discov 2004; 3: 499–508.

Mathews DT, Birney YA, Cahill PA, McGuinness GB. Mechanical and Morphological Characteristics of

Poly(vinyl alcohol)/Chitosan Hydrogels. Journal of Applied Polymer Science 2008; 109: 1129–1137.

Mincheva R, Manolova N and Rashkov I. Bicomponent aligned nanofibers of N- carboxyethylchitosan and

poly(vinyl alcohol). European Polymer Journal2007; 43: 2809–2818.

Masci G, Husu I, Murtas S, Piozzi A, Crescenzi V. Physical Hydrogels of Poly(vinyl alcohol) with Different

Syndiotacticity Prepared in the Presence of Lactosilated Chitosan Derivatives. Macromol. Biosci 2003; 3:

455–461.



Vol. 2, No. 1, 2013

40

Mattioli-Belmonte M, Gigante A, Muzzarelli RA, Politano R, De Benedittis A, Specchia N, Buffa A,

Biagini G, Greco F. N,N-dicarboxymethyl chitosan as delivery agent for bone morphogenetic protein in the

repair of articular cartilage. Med. Biol. Eng. Comput 1999; 37: 130–134.

Muzzarelli RAA, Biagini G, Belmonte MA, Talassi O, Gandolfi MG, Solmi R, Carraro S, Giardino R, Fini

M, NicoliAldini N. Osteoinduction by chitosan-complexed BMP: morpho-structural responses in an

osteoporotic model. J. Bioact. Compat.Polym 1997; 12: 321–329.

Ono K, Saito Y, Yura H, Ishikawa K, Kurita A, Akaike T, Ishihara M. Photocrosslinkable chitosan as a

biological adhesive. J. Biomed. Mater. Res 2000; 49: 289–295.

Park DJ, Choi BH, Zhu SJ, Huh JY, Kim BY, Lee SH. Injectable bone using chitosan alginate

gel/mesenchymal stem cells/BMP-2 composites. J. Cranio-maxillo-facial Surg 2005; 33: 50–54.

Prausnitz MR, Mitragotri S, Langer R. Current status and future potential of transdermal drug delivery. Nat

Rev Drug Discov 2004; 3: 115–124.

Pal K, Banthia AK, Majumdar DK. Preparation and Characterization of Polyvinyl Alcohol–Gelatin

Hydrogel Membranes for Biomedical Applications. AAPS Pharm. Sci. Tech2007; 8 (1): 21.

Pei HN, Chen XG, Li Y, Zhou HY. Characterization and ornidazole release in vitro of a novel composite

film prepared with chitosan/poly (vinyl alcohol)/alginate. J Biomed Mater Res 2008; 85A: 566–572.

Patel VR, Amiji MM. Preparation and characterization of freeze-dried chitosan/poly (ethylene oxide)

hydrogels for site-specific antibiotic delivery in the stomach. Pharm. Res 1996; 13: 588–593.

Ruel-Gariepy E, Shive M, Bichara A, Berrada M, Le Garrec D, Chenite A, Leroux JC. A thermosensitive

chitosan-based hydrogel for the local delivery of paclitaxel. Eur. J. Pharm. Biopharm 2004; 57: 53–63.

Rao KSVK, Naidu BVK, Subha MCS, Sairam M, Aminabhavi TM. Novel chitosan-based pH-sensitive

interpenetrating network microgels for the controlled release of cefadroxil.Carbohydrate Polymers2006; 66:

333–344.

Sung HW, Liang IL, Chen CN, Huang RN, Liang HF. Stability of a biological tissue fixed with a naturally

occurring crosslinking agent (genipin). J. Biomed. Mater.Res. 2001; 55: 538–546.

Sung HW, Huang RN, Huang LLH, Tsai CC. In vitro evaluation of cytotoxicity of a naturally occurring

cross-linking reagent for biological tissue fixation. J. Biomater. Sci. Polym. Ed 1999; 10: 63–78.

Suh JK, Matthew HW. Application of chitosan-based polysaccharide biomaterials in cartilage tissue

engineering: a review. Biomaterials 2000; 21: 2589–2598.

Sadeghi M, Yarahmadi M. Synthesis and characterization of superabsorbent hydrogel based on

chitosan-g-poly (acrylic acid-co-acrylonitrile). African Journal of Biotechnology 2011; 10(57):

12265-12275.

Sung JH, Hwang M, Kim JO, Lee JH, Kim YI, Kim JH, Chang SW, Jin SG, Kim JA, Lyoo WS, Han SS, Ku

SK, Yong CS, Choi HG. Gel characterisation and in vivo evaluation of minocycline-loaded wound dressing

with enhanced wound healing using polyvinyl alcohol and chitosan. International Journal of Pharmaceutics

2010; 392: 232–240.

Shu XZ, Zhu KJ. Controlled drug release properties of ionically cross-linked chitosan beads: the influence

of anion structure. Int. J. Pharm 2002; 233: 217–225.

Shigemasa Y, Minami S. Applications of chitin and chitosan for biomaterials. Biotechnol. Genet.Eng. Rev

1996; 13: 383–420.

Tsai CJ, Hsu LR., Fang JY, Lin HH. Chitosan hydrogel as a base for transdermal delivery of berberine and

its evaluation in rat skin, Biol. Pharm. Bull 1999; 22: 397–401.

Tan H, Chu CR, Payne KA, Marra KG. Injectable in situ forming biodegradable chitosan-hyaluronic acid

based hydrogels for cartilage tissue engineering. Biomaterials 2009; 30: 2499–2506.

Thanou M, Verhoef JC, Junginger HE. Chitosan and its derivatives as intestinal absorption enhancers. Adv.

Drug Deliv. Rev 2001; 50: S91–S101.



Vol. 2, No. 1, 2013

41

Tang Y, Du Y, Li Y, Wang X, Hu X. A thermosensitive chitosan/poly(vinyl alcohol) hydrogel containing

hydroxyapatite for protein delivery. J Biomed Mater Res 2009; 91A: 953–963.

Vrana NE, Liu Y, McGuinness GB, Cahill PA. Characterization of Poly(vinyl alcohol)/Chitosan Hydrogels

as Vascular Tissue Engineering Scaffolds. Macromol.Symp 2008; 269: 106–110.

Wang T, Turhan M, Gunasekaran S. Selected properties of pH-sensitive, biodegradable chitosan–poly

(vinyl alcohol) hydrogel. Polymer International2004; 53: 911–918.

Yokoyama F, Masada I, Shimamura K, Ikawa T, Monobe K. Morphology and structure of highly elastic

poly(vinyl alcohol) hydrogel prepared by repeated freezing-and-melting. Colloid Polym.Sci 1986; 264:

595–601.

Yang X, Liu Q, Chen X, Yu F, Zhu Z. Investigation of PVA/ws-chitosan hydrogels prepared by combined

γ-irradiation and freeze-thawing.Carbohydrate Polymers2008; 73: 401–408.

Yang JM, Su WY, Leu TL, Yang MC. Evaluation of chitosan/PVA blended hydrogel membranes. Journal of

Membrane Science 2004; 236: 39–51.

Yang SH, J. Lee YS, Lin FH, Yang JM, Che KS. Chitosan/Poly (vinyl alcohol) Blending Hydrogel Coating

Improves the Surface Characteristics of Segmented Polyurethane Urethral Catheters. J Biomed Mater Res

Part B: Appl Biomater 2007; 83B: 304–313.

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